The candidate is a promising young investigator with board certifications in Internal Medicine and Infectious Disease, and a Masters of Science degree in Clinical Investigation, who has made a substantial commitment to an academic career in patient-oriented research in aging and HIV. The career plan and research proposal are consistent with her long-term goal to become an independent clinical investigator, and leader in academic geriatric medicine and HIV. Older individuals represent an increasingly larger proportion of adults living with HIV infection in the United States. Reduced aerobic capacity, mitochondrial oxidative dysfunction and loss of lean muscle mass are problems that affect both HIV-infected and non-infected older adults. However sarcopenia and oxidative dysfunction may be more pronounced in the presence of HIV, with the deficits further compounded by the metabolic effects of antiretroviral therapy. Understanding the underlying mechanisms of limited functional performance in older HIV adults will allow us to design effective prevention and treatment strategies that will improve and preserve function in this rapidly growing older patient population. The objective of this proposal is to investigate the mechanisms by which aging affects physical functioning and aerobic capacity in HIV adults (AIM 1), and to determine if aerobic exercise training improves functional and cardiovascular performance in older HIV adults (AIM 2). Hypothesis #1. Reduced physical functioning with aging will be affected by baseline immune status in HIV adults, and will be similarly affected by medical comorbid conditions in HIV-infected vs. negative adults. Hypothesis #2. Skeletal muscle oxidative dysfunction is a central factor associated with reduced aerobic capacity and functional limitations in older HIV adults. Hypothesis #3. Aerobic exercise training will improve muscle oxidative dysfunction, and the associated functional limitations and reduced aerobic capacity in older HIV subjects compared to sedentary older HIV controls; however, improvements may be limited by the extent of sarcopenia and HIV-related myopathy. The proposed research will lay the foundation for subsequent studies that will investigate the optimal exercise-based rehabilitation strategies and the mechanisms by which they improve physical functioning in older HIV adults, and methods for their translation into community sites. [unreadable] [unreadable] [unreadable]